Candidate: Frederick M. Ivey, Ph.D. is an Assistant Professor in the Division of Gerontology, School of Medicine at the University of Maryland, Baltimore. The long-term career goal of the candidate is to advance academically in a research environment focusing on stroke, exercise, insulin-glucose metabolism, and cardiovascular risk factor modification. Dr. Ivey has recently joined the faculty in the Division, making this the ideal time in his career for this RCA to provide advanced research training in clinical and laboratory investigation. The candidate's immediate goat is to examine the mechanisms by which exercise afibcts atherothrombotic risk in chronic hemiparetic stroke patients under the guidance of experienced mentors. Background: Stroke is the leading cause of disability and thkd leading cause of death in the United States. Physical inactivity following stroke increases the incidence of hyperinsulinemia and the insulin resistance syndrome, which increases risk for recurrent stroke and MI by impairing endogenous fibrinoiysis and vasomotor function. Current strategies for preventing recurrent stroke and M1 are limited. Although aerobic exercise (AEX) improves fibrinolysis, nitric oxide-related vasomotor reactivity (NO-VMR), and insulin sensitivity in the healthy elderly, no prior studies have addressed the effects of AEX therapy on vascular endothelial celt function and insulin-glucose metabolism in chronic hemiparetic stroke patients. Our preliminary data provides the first evidence of improved endogenous fibrinolysis and reduced hyperinsulinemia in chronic hemiparetic stroke patients with AEX training. Hypothesis: In the proposed RCA the candidate investigates the hypothesis that 6 months treadmill AEX improves endogenous fibrinolysis and nitric oxide-related VMR in chronic hemiparetic stroke patients, and that these changes are related to improved insulin mediated glucose metabolism on both the whole body and tissue levels. The specific aims are to: 1) Determine the effects of 6 months AEX on a) fibrinolysis profiles and b) NO-VMR in the cerebral circulation. 2) Determine the effects of AEX on whole body insulin action, and whether alterations in fibrinolysis and NO-VMR are related to exercise-induced changes in insulin levels and action 3) Determine the effects of hemiparesis and AEX on insulin signaling proteins in stroke skeletal muscle. Environment: The Division of Gerontology has excellent resources for advanced research training in aging, stroke, exercise, metabolic, and vascular research. Additional training in molecular medicine is facilitated by Drs. Shuldiner and McLenithan, co-mentors on the revised proposal.